Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles.
The aim of the present study is to design and characterize quercetin-loaded solid lipid nanoparticles (QT-SLNs), clarify the absorption mechanism of QT-SLNs and to evaluate the potential of using solid lipid nanoparticles (SLNs) as an oral delivery carrier for poorly water soluble drugs. QT-SLNs were prepared by an emulsification and low-temperature solidification method. The QT-SLNs presented as spherically shaped under transmission electron microscopy, with an average diameter of 155.3 nm. The average drug entrapment efficiency, drug loading and zeta potential were 91.1%, 13.2% and -32.2 mV, respectively. Drug release from QT-SLNs was fitted to a double phase kinetics model and the equation was as follows: 100-Q=98.87e(-0.1042t)+42.45e(-0.0258t). The absorption of QT-SLNs in the gastrointestinal (GI) tract was studied using an in situ perfusion method in rats. It was found that the absorption percent in the stomach for 2 h was only 6.20%, the absorption process of intestine was first-process with passive diffusion mechanism, and the main absorptive segments were ileum and colon. A pharmacokinetic study was conducted in rats after oral administration of quercetin at 50 mg/kg in the form of either QT-SLNs or suspension. The plasma concentration-time curves were both fitted to a one-compartment model. The relative bioavailability of QT-SLNs to quercetin suspension was 571.4%. The T(max) and MRT for quercetin in plasma were both delayed. Our studies provide evidence that SLNs are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, quercetin.
Li
HouLi
H
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, China.
Zhao
XiaoBin
X
Ma
YuKun
Y
Zhai
GuangXi
G
Li
LingBing
L
Lou
HongXiang
H
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003106:Colon / Q000378:metabolism; D004337:Drug Carriers; D004386:Duodenum / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D005989:Glycerides / Q000737:chemistry; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D054709:Lecithins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011794:Quercetin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D004337:Drug Carriers; D005989:Glycerides; D054709:Lecithins; D008055:Lipids; C048159:glyceryl monostearate; D011794:Quercetin